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Treatment of Severe Multiple Sclerosis with High-Dose Immunosuppressive Therapy and Autologous Stem Cell Transplantation 2 Year Follow-Up



Treatment of Severe Multiple Sclerosis with High-Dose Immunosuppressive Therapy and Autologous Stem Cell Transplantation 2 Year Follow-Up



Blood 100(11): Abstract No 3408, November 16



Objective: To evaluate the stability of MS and safety of HDIT and autologous CD34-selected SCT with a median patient follow-up of 2 years. Methods: Autologous peripheral blood stem cells were mobilized with G-CSF (16 mug/kg/day) and CD34 selected using Isolex 300 (Nexell). HDIT consisted of TBI (800 cGy), cyclophosphamide (120 mg/kg) and ATGAM (90 mg/kg). Eligibility included an Extended Disability Status Scale (EDSS) score from 5.0-8.0 and an increase of one or more points in previous year. Twenty-one patients had failed previous therapy with interferon-beta and 15 had failed multiple therapies including copaxone, prednisone or methotrexate in addition to interferon. Results: Twenty-six patients (secondary progressive=17, primary progressive=8, relapsing-remitting=1), median age 41 (27-60) years were enrolled. Median EDSS at HDIT was 7.0 (5.0-8.0). Median follow-up was 29 (3-49) months. Early significant complications after HDIT were a MS flare during G-CSF for mobilization (n=1), EBV-posttransplant lymphoproliferative disorder (PTLD; n=1) and the engraftment syndrome (n=13). Late complications (>100 days) were infrequent. One patient developed a herpes simplex virus infection and 2 patients developed a varicella-zoster infection. All patients are now treated with antiviral therapy until 1 year after transplant. One patient developed hypothyroidism and another developed a Guillain-Barre syndrome and pneumonia at 12 and 17 months after HDIT and SCT, respectively. No secondary malignancies were observed. Of 25 evaluable patients, 6 have had an increase in the EDSS of gtoreq1.0 point (Kaplan-Meier (KM) estimate of progression at 2 years=27%). Four of these 6 patients progressed in the first year after HDIT. Three of 22 evaluable patients developed new or enhancing lesions on brain MRI after HDIT (including 1 related to G-CSF mobilization). Two deaths have occurred at day 53 from EBV-PTLD and at 23 months from bacterial pneumonia after continued progression of MS. The KM estimate of survival at 2 years was 91%. Conclusions: Late complications were infrequent after HDIT and SCT for severe MS. Although loss of neurological function continued in some patients, this was a heterogeneous group with advanced MS who had failed previous therapy. Treatment in earlier stages of MS possibly before the development of progressive disease may decrease the risk of continued loss of neurological function after HDIT. Controlled studies will be required to fully assess efficacy.

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Accession: 035980611

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